Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Adv Exp Med Biol. 2020;1243:21-40. doi: 10.1007/978-3-030-40204-4_2.
The cell cycle is a sophisticated space-time regulated mechanism where a wide variety of protein modules and complexes associate functioning in a concerted manner to regulate and transfer the genetic material to daughter cells. CCT (chaperonin containing TCP-1, also known as TRiC) is a molecular machine that forms a high molecular weight complex (1000 KDa). CCT is emerging as a key molecule during mitosis due to its essential role in the folding of many important proteins involved in cell division (Cdh1, Plk1, p27, Cdc20, PP2a regulatory subunits, tubulin or actin) suggesting its involvement in uncontrolled proliferation. The assembly is formed by eight different subunits called CCTα, β, γ, δ, ε, ζ, η and θ in mammals corresponding to CCT1-8 in yeast. CCT/TRiC is organized in a unique intra- and inter-ring arrangement. The chaperonin monomers share a common domain structure including an equatorial domain, which contains all the inter-ring contacts, most of the intra-ring contacts and the ATP binding site, whose binding and hydrolysis triggers the conformational changes that take place during the functional cycle. All chaperonins display an open substrate-receptive conformation, where the unfolded protein is recognized and trapped, and a closed conformation where the substrate is isolated from the bulk of the intracellular environment. In this chapter we discuss the complex set of intra- and inter-ring allosteric signals during chaperonin function.
细胞周期是一个复杂的时空调节机制，其中各种蛋白质模块和复合物以协调的方式结合在一起，以调节和将遗传物质转移到子细胞中。CCT（含 TCP-1 的伴侣蛋白，也称为 TRiC）是一种分子机器，它形成一个高分子量复合物（1000 kDa）。由于在细胞分裂过程中许多重要蛋白质的折叠中起着至关重要的作用，CCT 在有丝分裂期间成为关键分子（Cdh1、Plk1、p27、Cdc20、PP2a 调节亚基、微管蛋白或肌动蛋白），这表明其参与了不受控制的增殖。该组装由八个不同的亚基组成，称为 CCTα、β、γ、δ、ε、ζ、η 和 θ，在哺乳动物中对应于酵母中的 CCT1-8。CCT/TRiC 以独特的内环和外环排列方式组织。伴侣蛋白单体具有共同的结构域结构，包括赤道域，其中包含所有的外环接触、大部分的内环接触和 ATP 结合位点，其结合和水解引发功能循环中发生的构象变化。所有伴侣蛋白都显示出开放的底物接受构象，其中未折叠的蛋白质被识别和捕获，以及封闭的构象，其中底物与细胞内环境的大部分隔离。在本章中，我们讨论了伴侣蛋白功能过程中复杂的内环和外环变构信号。
